JAC Advance Access originally published online on April 6, 2006
Journal of Antimicrobial Chemotherapy 2006 58(1):220; doi:10.1093/jac/dkl143
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Correspondence |
Comment on Guidelines for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in the UK
Department of Medicine E, Beilinson Campus, Rabin Medical Center 49100 Petah-Tiqva, Israel
*Corresponding author. Tel: + 972-3-9376501; Fax: + 972-3-9376512; E-mail: leibovic{at}post.tau.ac.il
Keywords: Staphylococcus spp. , antibiotic policy , empirical treatment
Sir,
In the Guidelines for prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in the UK,1 the Joint Working Party states for empirical treatment that ‘The prevalence level at which flucloxacillin or other penicillinase-stable penicillins, in a patient group, becomes no longer the drug of choice is debatable, but 10% resistance has been used as a guide for avoiding the use of empirical gentamicin in Gram-negative infection and we would recommend the same threshold is used when contemplating treatment of staphylococcal infections with isoxazolylpenicillins or cephalosporins. This threshold may be adjusted depending on the apparent severity of infection.’
This threshold (of 10%) ignores the evidence that ß-lactam drugs are more effective than glycopeptides for infections caused by methicillin-susceptible S. aureus (MSSA) in the eradication of infection, prevention of recurrence and prevention of death.2–7 Moreover, it was impossible to show an advantage of glycopeptide appropriate empirical treatment over inappropriate treatment.8 The 10% threshold means that in order to offer appropriate treatment (vancomycin) to 10 patients with severe infections caused by MRSA, 90 people with severe infections caused by MSSA will be given less effective treatment (vancomycin and not cloxacillin).
To try and take this factor into account, we have looked at 429 patients with S. aureus bacteraemia included in the Beilinson Bacteremia Database.9,10 The fatality rate in patients given inappropriate empirical antibiotic treatment was 38% (69 of 183), versus 24% (57 of 246) in patients given appropriate treatment, P = 0.007. The multivariable-adjusted odds ratio was 1.8 [95% confidence interval (CI) 1.2–2.7].9 In patients with MSSA bacteraemia, the fatality rate was 28% (47 of 166) in patients treated with vancomycin versus 8% (4 of 48) in patients given cloxacillin, P = 0.004, univariate odds ratio of 4.3 (95% CI 1.5–12.8). The multivariable-adjusted odds ratio was larger than the univariate ones.
If indeed the advantage of cloxacillin over vancomycin as empirical treatment is at least as large as that of appropriate versus inappropriate treatment, the threshold of the baseline susceptibility to methicillin for preferring vancomycin over cloxacillin in a patient suspected of harbouring a severe infection with S. aureus should be 
50% rather than 10%.
Transparency declarations
We have no conflicts of interest to declare.
References
1
Gemmell CG, Edwards DI, Fraise AP, et al. (2006) Guidelines for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in the UK. J Antimicrob Chemother 57:589–608.
2 Siegman-Igra Y, Reich P, Orni-Wasserlauf R, et al. (2005) The role of vancomycin in the persistence or recurrence of Staphylococcus aureus bacteraemia. Scand J Infect Dis 37:572–8.[CrossRef][Web of Science][Medline]
3 Fortun J, Navas E, Martinez-Beltran J, et al. (2001) Short-course therapy for right-side endocarditis due to Staphylococcus aureus in drug abusers: cloxacillin versus glycopeptides in combination with gentamicin. Clin Infect Dis 33:120–5.[CrossRef][Web of Science][Medline]
4 Apellaniz G, Valdes M, Perez R, et al. (1991) Comparison of the effectiveness of various antibiotics in the treatment of methicillin-susceptible Staphylococcus aureus experimental infective endocarditis. J Chemother 3:91–7.[Medline]
5 Chang FY, Peacock JE Jr, Musher DM, et al. (2003) Staphylococcus aureus bacteremia: recurrence and the impact of antibiotic treatment in a prospective multicenter study. Medicine (Baltimore) 82:333–9.[Medline]
6 Gentry CA, Rodvold KA, Novak RM, et al. (1997) Retrospective evaluation of therapies for Staphylococcus aureus endocarditis. Pharmacotherapy 17:990–7.[Web of Science][Medline]
7 Johnson LB, Almoujahed MO, Ilg K, et al. (2003) Staphylococcus aureus bacteremia: compliance with standard treatment, long-term outcome and predictors of relapse. Scand J Infect Dis 35:782–9.[CrossRef][Web of Science][Medline]
8
Fang CT, Shau WY, Hsueh PR, et al. (2006) Early empirical glycopeptide therapy for patients with methicillin-resistant Staphylococcus aureus bacteraemia: impact on the outcome. J Antimicrob Chemother 57:511–9.
9 Leibovici L, Shraga I, Drucker M, et al. (1998) The benefit of appropriate empirical antibiotic treatment in patients with bloodstream infection. J Intern Med 244:379–86.[CrossRef][Web of Science][Medline]
10
Leibovici L, Samra Z, Konigsberger H, et al. (1995) Long-term survival following bacteremia or fungemia. JAMA 274:807–12.
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